CNSE Associate Professor
of Nanobioscience
Dr. Mohamed Trebak

Game-changing nanobioscience research conducted at SUNY’s College of
Nanoscale Science and Engineering (CNSE) is gaining global recognition,
serving as the impetus for a cover story in Science Signaling magazine, as well as being highlighted in Science magazine, while a separate discovery has also been featured as the cover story in Circulation Research.

CNSE Associate Professor of Nanobioscience Dr. Mohamed Trebak and a team
of CNSE graduate students and postdoctoral researchers, working in
collaboration with scientists at Albany Medical College and Tulane
University, received recognition from Science Signaling for
discovering that the STIM1 protein, which is typically thought to be a
sensor for calcium ions inside the cells, can also control the
cytoskeleton of endothelial cells independently of its previously known
functions.

Endothelial cells form the inner layer of blood vessels and make direct
contact with blood flow. The control of the endothelial cells’
cytoskeleton can cause the cells in the endothelial layer to contract
and shrink, creating gaps in the endothelial layer to allow movement of
fluids and cells. This phenomenon, which promotes vascular leakage into
the neighboring tissue, could play a major role in the diagnosis and
treatment of diseases ranging from inflammation and sepsis to diabetes
and cancer.

Science Signaling Magazine

The findings were documented in a research article entitled, “STIM1 Controls Endothelial Barrier Function Independently of Orai1 and Ca2+ Entry,” which was featured as the cover story in the March 19 issue of Science Signaling,
the foremost journal for announcing major advances related to the
understanding of cell signaling. It is published by the American
Association for the Advancement of Science (AAAS), an international
non-profit organization dedicated to advancing science around the world.

The editors, in conjunction with a Board of Reviewing Editors and other
in-depth reviewers, selected the paper for publication based on its
importance and broad interest to scientists. As part of the cover story,
prominent scientists highlighted the team’s pioneering work in an
accompanying perspective in the same issue of Science Signaling.
Meanwhile, a research summary has also been featured in an issue of
Science magazine under the “Editors’ Choice” banner.

Dr. Trebak’s research paves the way for further advancements in the
diagnosis and treatment of many diseases precipitated by the behavior of
the STIM1 protein, which might someday represent a promising target for
drug therapies.

“This research opens a new world of possibilities. When you are armed
with this knowledge, further study may allow us to modify the behavior
of STIM1 so as to mitigate or modify its function within the cell for
therapy purposes,” said Dr. Trebak. “For example, we might be able to
inhibit angiogenesis, the process of growing new blood vessels which is
required for cancer cells to proliferate, and this would effectively
prevent cancer cell growth. It’s just one way in which our novel
discovery could eventually lead to improved future outcomes for patients
who suffer from serious diseases.”

Dr. Trebak is hopeful that this research will inspire further scientific
inquiry into the exact role of STIM1 proteins related to their
interactions with endothelial cells and provide a more intimate
understanding of the processes involved in vascular leakage.

“There is additional molecular work that will be undertaken to fine-tune
what we have found, including the study of the STIM1 protein’s exact
domains that are required for this novel function,” he said. “This will
help us gain a clearer picture of which pathways to specifically target
so as to bring about the best outcome in the fight against these various
diseases.”

Highlighting the significance of this work, Circulation Research,
published by the American Heart Association, not only included the
research paper as its cover story, but also in its “Editorials” and “In
this issue” sections. The team’s work was also chosen as the “Editor’s
Pick” for its state-of-the-art approach to illuminate human disease
mechanisms.

The research paper focuses on their discovery of a novel protein channel
target, Orai3/Orai1 activated by leukotrieneC4, that can be used to
stop neointima, or the remodeling of vessels after disease or injury.
This “faulty” remodeling can cause blockages and lead to further
vascular complications. By using a combination of molecular tools and
surgeries, the team has shown that this newly found channel could
represent a specific target for future therapy of major cardiovascular
diseases.

“This groundbreaking research discovered a molecular pathway involved in
the uncontrolled growth of the layer of smooth muscle which is relevant
to diseases like restenosis, atherosclerosis, hypertension, stroke, and
a very rare form of smooth muscle cancer that isn’t very well known,
called leiomyosarcoma,” said Dr. Trebak. “Now the key is to investigate
in greater detail the precise regulation of these molecules within the
cells to find out what kind of hormones or neurotransmitters or growth
factors can control these proteins that can lead to their upregulation
or downregulation. That way we can control their activity, thus
providing us with a new path toward improved therapies with fewer side
effects for people who suffer from these diseases and complications.”